Table 1.
Synergism of co-delivery of therapeutics to enhance efficacy of cancer therapy.
| Therapeutics | Application | Explanation of synergistic effect | Ref |
|---|---|---|---|
| Drug/Drug | |||
| Doxorubicin and Combrestatin | Cancer | Combrestatin is a vascular disrupting agent that targets the tumor blood vessels, causing tumor vasculature shutdown, trapping DOX in the tumor. | 4 |
| Doxorubicin and Verapamil | Cancer | Verapamil is a calcium channel antagonist which also acts as a P-gp inhibitor. This increases the cell sensitivity and DOX accumulation within the cell. | 5 |
| Heparin with Taurocholate (LHT7) and Suberoylanilide hydroxamic acid (SAHA) | Cancer | LHT7 is an anti-angiogenic drug. SAHA causes cell cycle arrest, angiogenesis. Together they inhibit angiogenesis and cell proliferation. | 6 |
| Fluoroorotic acid and Irinotecan | Cancer | Irinotecan inhibits DNA re-ligation by inhibiting topoisomerase 1, and fluoroorotic acid inhibits DNA synthesis. | 7 |
| Cyclophosphamide and Doxorubicin | Cancer | Cyclophosphamide increases permeability of tumor micro vessels, leading to increased DOX accumulation in the tumor. | 8 |
| Vincristine and Topotecan | Cancer | Topotecan acts in the S-phase or G2-M phase by converting DNA topoisomerase 1 to a cellular toxin, and vincristine leads to mitotic arrest by depolarizing the microtubules. | 9 |
| Doxorubicin and Paclitaxel | Cancer | DOX bound to DNA prevents formation of tubulin, and paclitaxel degrades existing microtubules. | 10 |
| Drug/siRNA | |||
| Doxorubicin and Bcl-2 siRNA | Cancer | Bcl-2 induces an anti-apoptotic signal and DOX induces apoptosis. Knockdown of Bcl-2 with siRNA allows DOX to function more efficiently. | 11 |
| Doxorubicin and P-gp siRNA | Cancer | Knockdown of P-gp, a MDR-contributing gene, restores the sensitivity of the cancer cell to DOX. | 12 |
| Doxorubicin and Plk-1 siRNA | Cancer | Plk-1 is a regulator of mitotic progression in mammalian cells. Knockdown of the gene along with DOX delivery induces a clear synergistic effect. | 13 |
| Drug/Plasmid | |||
| Doxorubicin and pORF-hTRAIL gene | Cancer | TRAIL causes apoptosis by transmitting apoptotic signals through an extrinsic pathway. DOX causes DNA damage through intrinsic pathway. | 14 |
| Doxorubicin and Survivin mutant gene | Cancer | Survivin leads to increased resistance against DOX. The plasmid is a strong negative mutant of survivin which aims to reduce the resistance. | 15 |
| Paclitaxel and pEGFP-hTRAIL gene | Cancer | TRAIL targets cancer cells over normal cells but glioma gains resistance very quickly. PTX makes the cells more sensitive to TRAIL-induced apoptosis due to crosstalk between intrinsic and extrinsic pathways. | 16 |
| Doxorubicin and p53 antitumor gene | Cancer | DOX is a chemotherapeutic and p53 enhances sensitivity of cells to the chemotherapeutics. | 17 |